Abstract
Advances in the molecular characteristics of cancers have facilitated the classification system from morphology to molecular characteristic-based subtypes. Cancer profiling has expanded in its focus from protein-coding genes to noncoding RNAs, with advances in the depth and quality of transcriptome sequencing. Here, we examined the profiles of long noncoding RNAs (lncRNAs) according to breast cancer subtype categories in The Cancer Genome Atlas (TCGA) database to identify a cohort of breast cancer- and oestrogen receptor (ER)-negative-associated lncRNAs. According to the prioritization of variation in ER-negative-associated lncRNAs, we identified and investigated the role of LINC00511 in breast cancer. We determined that high LINC00511 expression was an unfavourable prognostic factor for patients with breast cancer. Furthermore, LINC00511 promoted tumour growth by accelerating the G1/S transition and inhibiting apoptosis. At the transcriptional level, ER deficiency directly affected the expression of LINC00511 activated by transcription factor AP-2 (TFAP-2) in breast cancer cells. Moreover, mechanistic investigations demonstrated that ER-negative-associated LINC00511 interacted with enhancer of zeste homologue 2 (EZH2, the catalytic subunit of polycomb repressive complex 2, PRC2) and recruited PRC2 to mediate histone methylation, contributing to the repression of CDKN1B in the nucleus. This process resulted in altered ER-negative breast cancer cell biology. By highlighting the oncogenic function of LINC00511, we revealed the role of lncRNAs in regulating the network of cell cycle control in ER-negative breast cancer and suggested the exploitation of LINC00511 as an anticancer therapy in the future.
Highlights
Breast cancer is one of the most commonly diagnosed cancers and the leading cause of death in women worldwide[1]
We demonstrated that ER deficiency directly affected the expression of LINC00511 activated by transcription factor AP-2 (TFAP-2) and identified EZH2, which is involved in histone methylation, as a protein that interacts with LINC00511 and contributes to the repression of CDKN1B in ER-negative breast cancer
Utilizing the large-scale cancer genome RNA-seq expression data from the The Cancer Genome Atlas (TCGA) database, we focused on the potential carcinogenesis of long noncoding RNAs (lncRNAs) that were differentially expressed in breast cancer tissues compared with adjacent normal tissues
Summary
Breast cancer is one of the most commonly diagnosed cancers and the leading cause of death in women worldwide[1]. With advances in the recognition of the molecular characteristics of cancers, breast cancer has been categorized into four major subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-positive and basal-like[2,3]. Among the major molecular characteristics of breast cancer, oestrogen receptor (ER) is. Long noncoding RNAs (lncRNAs) are heterogeneous categories of transcripts more than 200 base pairs in length. Because they lack the ability to translate into proteins, they were once considered “transcriptional noise”[9,10]. Zhang et al Cell Death and Disease (2019)10:599 confirmed to be involved in multiple pathological conditions such as carcinogenesis and cancer progression[11,12,13]. Interaction probabilities Input Positive Control Negative Control LINC00511 Antisense-LINC00511 c EZH2 HuR h
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